The genus Agaricus Linnaeus 1753 belongs to family Agaricaceae (Basidiomycota) and comprises over 200 species in its current circumscription (Kirk et al. 2008, Ainsworth & Bisby's dictionary of the Fungi, Tenth Edition, Wallingford, p. 13-14), many of which are edible mushrooms. They are saprotrophic and occur in natural habitats such as meadows and forests, but even in habitats heavily influenced by humans all over the tropical and temperate climates of the world. Several species of Agaricus, such as the Button Mushroom, Agaricus bisporus, can be cultivated on commercial scale and are being sold as food all over the world. The genus is divided into sections, according to morphological (habit of the fruiting bodies, morphology of basidia, basidiospores, and cystidia), and chemotaxonomic (odour, colouring reactions upon injury) characteristics. This classification was recently confirmed and stabilized by using molecular phylogenetic methods, which also allowed for safely establishing the synonymy of certain species that have been described independently by different mycologists from different parts of the world. In particular nuclear ribosomal desoxyribonucleic acid (nrDNA) data, and preferable the 5.8S/ITS regions, are being widely used to characterize fungal species. The availability of universal PCR primers for amplification of fungal nrDNA (White, T. J. et al. 1990. In: PCR Protocol: A Guide to Methods and Applications. Eds. M. A. Innis et al. Academic Press, New York. pp. 315-322) has even facilitated sequencing of old herbarium specimens, and the work on the taxonomy and phlyogeny of Agaricus cited below also relied on such methods. The genus Agaricus is traditionally being divided in several sections, of which section Arvenses (which includes Agaricus subrufescens and several other edible mushrooms, such as Agaricus arvensis) is the most important in relation to this invention. Other important sections include e.g., sect. Xanthodermatei (including most of the toxic species in Agaricus; see Kerrigan et al., Mycologia (2005) 97: 1292-1315 and sect. Bivelares (including Agaricus bisporus; see Kerrigan et al., Mycologia, (2008) 100: 876-892), and sect. Agaricus, including the type species, the edible horse mushroom, Agaricus campestris. The species included in those sections are not subject of the present invention, as they can apparently not produce the beneficial compounds.
A world-wide renowned expert in the taxonomy, Kerrigan (Mycologia (2005) 97(1): 12-24), has recently summarized the taxonomic history of Agaricus subrufescens, and his study was validated by morphological studies of type specimens, as well as by molecular phylogenetic studies on various representatives that have been treated as Agaricus subrufescens or synonyms of this name. In this publication, the currently valid name is given as Agaricus subrufescens Peck, New York State. Mus. Ann. Rep. (1893) 46:105. The basionym of this name is Psalliota subrufescens Kauff. The Agaricaceae of Michigan (1918) 239. Accepted synonyms are Agaricus rufotegulis Nauta Persoonia (1999) 17: 230 and Agaricus brasiliensis Wasser, Didukh, de Amazonas & Stamets. Int. J. Med. Mush. (2002) 4:274. Since nomenclature and taxonomic aspects are important to understand the scope of the current invention, their taxonomic history of the respective Agaricus species is explained in detail further below.
The species Agaricus blazei Murill was erected by the American mycologist Murrill (1945), based on material collected in Florida, USA and named for the collector of the specimen, whose surname was Blaze. The name Agaricus blazei was eventually used by the Belgian mycologist Heinemann for a fungus from Brazil with medicinal properties that has since then been widely referred to as Agaricus blazei in the literature. However, Wasser et al. (Int J Med Mush (2002) 4: 267-290) demonstrated that this name was misapplied by Heinemann, who have obviously misidentified the medicinally important species. According to their meticulous morphological studies on type and authentic material of both species, it became clearly evident that Agaricus blazei differed from the Brazilian fungus referred to as “Agaricus blazei” by Heinemann (Bull Jard Bot Belgium (1993) 62: 365-368) in the morphology of its fruiting bodies, the microscopic characters of the pileal covering, the presence of cheilocystidia on the lamellae, and in its basidiospore size. All these characters are regarded as valid criteria for differentiation of species in the genus Agaricus, and if two given taxa in the genus Agaricus differ in all four characteristics mentioned, it can be assessed with certainty that they represent two different species.
The name “Agaricus blazei Murrill” sensu Heinemann (1993) should therefore not be used anymore to characterize the economically important fungus, for which Wasser et al. (2002) had proposed a new name, Agaricus brasiliensis. 
Wasser et al. (Intl J Med Mush (2002) 4: 267-290) further proposed that Agaricus blazei sensu stricto is a rare, endemic species of North America that has been collected rather infrequently in Southeastern USA. The medicinal properties of Agaricus blazei sensu stricto are unknown. There are no reports in the literature suggesting with certainty that this fungus has ever been cultivated, and it even remains unclear whether Agaricus blazei actually constitutes an edible species.
On the other hand, Kerrigan (Mycologia (2005) 97(1): 12-24) has meanwhile shown conclusively by using morphological and molecular phylogenetic data, as well as mating studies, that Agaricus brasiliensis and Agaricus subrufescens are synonyms. Accordingly, the erection of the species Agaricus brasiliensis was superfluous, since the older name, Agaricus subrufescens, takes preference over Agaricus brasiliensis, according to the current rules of the International Botanical Code.
According to Kerrigan (2005) Agaricus subrufescens is also a species that was first described from New York State, USA, where it was already cultivated in the 19th century on a commercial scale, long before it was first found in Brazil or used as medicinal mushroom in Asia. This means that the economically important fungus is not an exotic, tropical species as had hitherto been assumed by many authors, but has actually been used as food in the Western civilization for over a century. Kerrigan (2005) further reported Agaricus subrufescens or synonymous species from Europe, Asia, Hawaii, North and South America, even though it remains unclear which of these records might relate to strains that escaped from cultivation plants into the environment, and which of them would relate to the original geographic distribution of this mushroom.
While all experts appear to agree that the name Agaricus blazei should no longer be used for the Brazilian medicinal mushroom, the problem of synonymy of Agaricus brasiliensis and Agaricus subrufescens is still under discussion. Wasser et al. (Int J Med Mushrooms (2005) 7: 507-511) and Kerrigan (Int J Med Mushrooms (2007) 9(1): 79-83) have both brought forward arguments to justify their taxonomic opinion, relying on different species concepts. A very convincing argument brought forward by Kerrigan is that “single-spore progeny of A. subrufescens from North America and another strain from Brazil (by way of Japan) can mate to produce fertile offspring”, hence they are synonyms according to a biological species concept, as it is commonly applied in animals and plants.
However, regardless of the taxonomic opinion, there is a problem in nomenclature associated with the use of the name Agaricus brasiliensis, sensu Wasser et al., since the same name has been used previously by other mycologists to describe a different fungus. Agaricus brasiliensis Fr. 1830 is listed in the databases Mycobank and Index Fungorum (www.mycobank.org & www.indexfungorum.org), two databases on fungal taxonomy and nomenclature that are being maintained by renowned taxonomic experts, as the oldest record of this name, which was already used in 1830 by the Swedish mycologist, Elias Fries. Therefore, the name A. brasiliensis Wasser et al. constitutes a later homonym and appears to be illegitimate, according to the rules of the International Botanical Code. Accordingly, it has therefore been listed as illegitimate in Mycobank.
All the above names, their interpretations in the cited literature and their synonyms, in particular including the medicinal fungus that is now still often named Agaricus blazei, or occasionally, Agaricus brasiliensis, will therefore henceforth be referred to as Agaricus subrufescens, following the taxonomic concept proposed by Kerrigan outlined above, to avoid ambiguities.
As molecular techniques were more widely employed in all disciplines of biology, large databases were created on the Internet to allow scientists to deposit their DNA, RNA, and protein sequences in order to facilitate comparison of such data. This also holds true for ribosomal DNA sequences, which are in widespread use for characterization of fungal organisms and are increasingly used to verify and refine taxonomic and phylogenetic concepts. These databases, such as GenBank (www.ncbi.nlm.nih.gov/genbank) and EMBL (www.embl.de), are particularly helpful in many aspects of modern natural science, so long as the data deposited therein can be considered reliable and genuine. However, it should be noted that it is the depositors' responsibility to provide correct identifications of the species when depositing such DNA sequence data in the afore mentioned Internet databases, which therefore contain many data of poorly characterized or even misidentified specimens. This problem has been addressed, with particular emphasis on fungi, by Bridge et al. New Phytologist (2003) 160: 43-48. These sequences can be identified by comparison of their similarity with other DNA sequence data derived from material that was thoroughly studied and may therefore be regarded as genuine. For instance, regarding Agaricus subrufescens sensu Kerrigan (2005), all DNA sequence data of ITS/5.8S ribosomal DNA which the author found to correspond with his morphological species concept, showed also a high similarity to one another in the concurrent phylogenetic tree. There are, however, sequences that appear to belong to this group of Agaricus subrufescens sensu Kerrigan, which were deposited under different names. For instance, this includes the sequence of a fungus named “Agaricus sylvaticus” by Huang and Hseu (Taiwanese Journal of Agricultural Chemistry and Food Science 2004, 42: 75-82), which was derived from a strain that was sent to the authors as a gift by a Japanese colleague, but no details on the origin and the means of identification was reported. The DNA sequence data derived from this strain were deposited with GenBank as acc. no AJ133375, and the authors reported similarities to Agaricus blazei. As Agaricus sylvaticus belongs to section Sanguinolenti, which is generally regarded by all taxonomists acquainted with the genus Agaricus as rather distantly related to sect. Arvenses and Agaricus subrufescens sensu strictu, the DNA sequence data published by Huang and Hseu are probably derived from a misidentified isolate that may actually correspond with Agaricus subrufescens, rather than Agaricus sylvaticus. 
Even among the closest relatives of Agaricus subrufescens, i.e., the species accommodated in Agaricus, section Arvenses, some species have probably been confused with Agaricus subrufescens sensu Kerrigan (2005), before this author published his conclusive study involving DNA sequencing of type material. The taxonomic concept of Agaricus subrufescens had not been clear prior to the study by Kerrigan (2005). Geml J. et al. (Mycol Progress (2004) 3:157-176) have classified some isolates as Agaricus subrufescens, (e.g. the specimen with corresponding GenBank acc, no AY484674) which do apparently not correspond to the current species concept proposed by Kerrigan (2005). The fact that they also included Agaricus blazei in their study suggests that they employed a different species concept from that developed later by Kerrigan (2005), on which the present invention relies.
Liver X receptors (LXR) are nuclear hormone receptors that play a critical role in cholesterol homeostasis. LXR agonists are expected to increase cholesterol efflux, lower LDL (the “bad” cholesterol) and raise HDL (the “good” cholesterol) levels (see Zelcer N et al., Curr. Opin. Investig. Drugs. 2005 6(9): 934-943, and Geyeregger R et al., Cell. Mol. Life Sci. 2006 63(5): 524-539). Known LXR agonists were discovered by screening libraries from natural sources and proof of principle in animal models was possible (see Herath K B, et al., J. Nat. Prod. 2005 68: 1437-1440; Jayasuriya H et al., J. Nat. Prod. 2005 68: 1247-1252; and Singh S B et al., Bioorg. Med. Chem. Lett. 2005 15(11): 2824-2828). LXR agonists have also been shown to modulate (especially inhibit) immune and inflammatory responses, especially in macrophages (see e.g. Zelcer, N., et al., J. Clin. Invest. 116(3), 607-614 (2006)).
Two LXR genes have been identified, LXRα and LXRβ (also known as NR1H3 and NR1H2, respectively). The LXRβ is expressed ubiquitously, whereas the LXRα expression is mainly restricted to tissues known to play an important role in lipid metabolism (liver and adipocytes). In addition, human skeletal muscle cells have higher levels of LXRβ than LXRα (Kase et al., Diabetologia 50(1), 2171-2180 (2007).
The protein family of Liver X Receptors (LXRs) was originally identified as orphan (unknown ligand) members of the nuclear receptor superfamily. As other family members, LXRs hetero-dimerize with retinoid X receptor and bind to specific response elements (LXREs). Two protein variants, alpha (LXRA; NR1H3) and beta (LXRB; NR1H2), are known (Song et al., Ann. N.Y. Acad. Sci. 761: 38-49, 1995). LXR-alpha and LXR-beta regulate the metabolism of several important lipids, including cholesterol in bile acids. It was proposed that naturally occurring oxysterols are physiological ligands of LXRs triggering regulation of these pathways (Janowski et al., Proc Natl Acad Sci USA. 5; 96(1):266-71, 1999).
LXRs have in the arts been considered as established regulators of cholesterol, lipid and glucose homeostasis (Li and Glass, J. Lipid Res. 45, 2161-2173, 2004). Moreover LXRs are described in the arts as highly expressed in adipose tissues and to be involved in white/brown fat tissue differentiation (Hansen and Kristiansen Biochem J. (2006) 398(2): 153-68). In mature adipocytes, activation of LXR was described in the art as inducing expression of genes involved in lipid and glucose homoeostasis (Laffitte et al. Proc. Natl. Acad. Sci. U.S.A. (2001) 98: 507-512162; Laffitte et al. Proc. Natl. Acad. Sci. U.S.A. (2003) 100: 5419-5424163; Dalen et al. Biol. Chem. (2003) 278: 48283-48291; Ulven et al. J. Lipid Res. (2004) 45: 2052-2062).
LXRbeta has been described as regulator of Uncoupling Protein 1 (UCP1) expression. LXRα−/−/LXRβ−/− mice exhibited enhanced energy dissipation due to ectopic expression of UCP1 in WAT and muscle while administration of LXR agonist to mice suppresses UCP1 expression in BAT (Stulnig Mol. Pharmacol. (2002) 62: 1299-1305). UCP1 is involved in thermogenesis (thermoregulation) and enhanced energy expenditure.
LXRα−/−/LXRβ−/− mice were in the art found to be resistant to diet-induced obesity when fed a western high-fat high-cholesterol diet, but not when fed a cholesterol-free high-fat diet. In the art, LXR agonists have been described as potential therapeutic agents for treatment of dyslipidemia and thereby metabolic syndrome, coronary artery disease, and atherosclerosis due to their anti-atherogenic and HDL-raising properties (Lund et al. Arterioscler. Thromb. Vasc. Biol (2003) 23: 1169-1177; Beaven and Tontonoz Ann Rev Med. (2006) 57: 313-29; Baranowski J Physiol Pharmacol (2008) 59, Suppl7, 31-55; Sanal World J Gastroenterol. (2008) 14(6): 831-44). Moreover, it has been described in the arts that LXRs are involved in fatty liver disease (Sanal M G. 2008; Beaven and Tontonoz, 2006). Furthermore LXR ligands have been described in the arts as efficient in models of type 2 diabetes and have been claimed as useful insulin sensitizers for treatment of insulin resistance (Commerford et al. Mol Endocrin (2007) 21(12): 3002-301; Baranowski, 2008).
Synthetic oxysterol-mimetic drugs (LXR agonists) have also been described as novel therapeutics for management of Alzheimer's Disease and other neurological afflictions characterized by deranged tissue cholesterol homeostasis (Vaya and Schipper J Neurochem. (2007) 102 (6):1727-37). LXR modulators have been discussed as potential targets for pharmacological intervention in cardiovascular diseases and potential cardioprotectants (Cao et al. Drug News Perspect (2004) 17(1): 35-41; Schmitz and Drobnik Curr Opin Investig Drugs. (2002) 3(6): 853-8). LXR agonists have further been described as anti-inflammatory drug candidates (Joseph et al. Nat Med (2003) 9: 213-219) Moreover LXR receptor agonists are described in the arts as protecting against neuronal damage following global cerebral ischemia while providing neuroprotection in inflammatory cerebral conditions via inhibition of NfkappaB (Cheng et al. Neuroscience (2010) 14; 166(4):1101-9).
“Medicinal mushrooms” have traditionally been used as “herbal” remedies in Asian folk medicine for over 300 years, comprising a substantial part of the so-called Traditional Chinese Medicines (TCM), for their therapeutic effects in various disease areas. Our current knowledge on these fungi has been summarized in various reviews (Chang, Int J Med Mushrooms (2006), 8: 187-195; Lindequist et al., Medizinische Monatsschrift Pharmazeuten (2010), 33: 40-48; Wasser, Int J Med Mushrooms (2010) 12: 1-16). Many important fungal species that have been traditionally used in Asia as therapeutic agents (for example, Cordyceps sinensis, Ganoderma lucidum, Trametes versicolor) are not considered edible in the Western world, as their sporocarps have a rather tough, non-fleshy consistence. Nonetheless, they are being increasingly cultivated even in Europe and America for preparation of traditional “herbal” remedies, food supplements and ingredients for cosmetics. Mushroom powders, as well as aqueous and organic extracts made from these organisms are being sold world-wide with increasing commercial success. Other “medicinal mushrooms” like Hericium erinaceus and Lentinula edodes, are being grown at a very large scale and sold for culinary as well as for medicinal purposes. Interestingly, species of the genus Agaricus, which had been successfully cultivated as food for over a century in the Western world, do not belong to these traditional “herbal” medicines of Asian origin. However, researchers in Japan and other Asian countries have evaluated the medicinal properties of edible mushrooms from other parts of the world in the past decades, along with their own indigenous species. Accordingly, they also found beneficial effects in certain species from America and Europe. Some of them have meanwhile reached significant commercial value as “medicinal mushrooms” in Asia, despite they are not included in any ancient Pharmacopoeia. One such example is Agaricus subrufescens, which is still most often referred to in the scientific and trivial literature as “Agaricus blazei”. According to the current knowledge, the strains that are currently being studied for medicinal properties are derived from material that had originated from Brazil, from where it was transferred to Asia by Japanese researchers and evaluated there during the last decades of the 20th century for beneficial effects and chemical constituents.
Owing to their great economical importance, many species of the genus Agaricus have been targeted extensively for studies on their chemical constituents. In particular the fruiting bodies have been screened for the presence of toxins and metabolites of potential benefits. Far less information appears to be available on the secondary metabolites of Agaricus cultures. Stadler et al. (J. Antibiot. 58, 2005, 775-786) reported a series of triglycerides of chlorinated phenols with potential analgesic effects, owing to their strong inhibitory activity against neurolysin, from cultures of Agaricus macrosporus and several other species of the genus Agaricus. Aside from the triglycerides, which were named agaricoglycerides, simple chlorinated aromatics such as 3,5-dichloroanisic acid were also obtained. Neither the agaricoglycerides nor the other aromatic compounds were identified in the corresponding fruiting bodies from which the cultures producing agaricoglycerides had been made. On the other hand, under the chosen fermentation conditions, the dichloro anisic acids were prevalent in the cultures of several Agaricus strains, including such ones that did not produce agaricoglycerides. These results have shown that the secondary metabolism of Agaricus species in fruiting bodies versus mycelial cultures can be completely different.
Indeed, the characteristic secondary metabolites that are hitherto known from fruiting bodies of many Agaricus species include aromatic nitrogen containing quinones, hydrazone derivatives and related compounds (see overview by Gill and Steglich, 1987, Progress in the Chemistry of Natural Products, Vol. 51, Chapter 6, p. 236f.). The most important compound of the hydrazone type appears to be N2-(gamma-L-glutamyl)-4-hydroxymethyl-phenylhydrazine; trivial name: agaritine), which has been detected in substantial quantities even in many edible species of Agaricus (see review by Roupas et al., Journal of Functional Foods 2, 2010, 91-98). This compound is known to have toxic effects, as it is converted into carcinogenic metabolites in the mammalian body. Therefore, it has been discussed to be a potential hazard for the therapy of diseases in humans using fruiting bodies of Agaricus species as “medicinal mushrooms. Using the invalid species name “Agaricus blazei”, Firenzuoli et al. (Evidence-based Complementary and Alternative Medicine (2008) 5(1): 3-15) have recently discussed this problem in Agaricus subrufescens, which also belongs to the species of Agaricus that contain agaritine in their basidiocarps.
They reasoned that the potential carcinogenic effects of agaritine are controversial to those of the beta glucanes that are also produced in the fruiting bodies of Agaricus subrufescens and have been made responsible for cancer prevention and manifold other beneficial biological activities. Most of the recent results have been summarized by Sorimachi & Koge (2008) Current Pharmaceutical Analysis, 4 (1), pp. 39-43.
According to this review and the references cited therein, the aqueous extract of the fungal sporocarps has been demonstrated both in vivo and in vitro to have: Antitumor, immunostimulating, anti-genotoxic, anti-mutagenic and anti-clastogenic and antiviral activity.
The cultured mycelia of the fungus also contain beta-glucane polysaccharides with similar beneficial activities and are being produced at large scale by fermentation of Agaricus subrufescens in Asia. Several working groups in Asia, such as Kawagoe et al. (J Chem Eng Japan, (2004) 37 (8 SPEC. ISS.): 1056-1061), Kim et al. (J Microbiol & Biotechnol, (2004) 14: 944-951), Lin and Yang (J Microbiol, Immun and Infection, (2006) 39: 98-108) have been studying the optimization of their production in submerged culture, which they proposed to be taken as substitute for the relatively expensive fruiting bodies. Accordingly, Lin and Yang (2006) measured the crude polysaccharide content of the mycelia during fermentation. Fan et al. (LWT—Food Sci Technol, (2007) 40: 30-35) even used biological assays in addition to other analytic methods to quantify the biologically active polysaccharides. Na et al. (J Microbiol & Biotechnol, (2005) 15: 1388-1391) have studied the growth and production of such macromolecules in submerged culture of A. subrufescens. They found that the addition of yeast extract along with glucose during fermentation of the fungus has a positive effect on cell growth and production of beta-glucanes and proposed a method for fed-batch fermentation of the fungus to optimize glucan production.
In general, all other published optimization experiments for A. subrufescens in submerged culture appear to have been directed towards the yields of mycelia, or beta-glucanes and other macromolecular, hydrophilic, biologically active agents contained therein.
In this context, it is important to note that the evidence provided by Mizuno et al. (Biochem & Molecular Biology Int, (1999) 47: 707-714) and Hashimoto et al. (Int J Med Mushrooms, (2006) 8: 329-341) strongly suggests that the polysaccharides produced in cultured mycelium of A. subrufescens are entirely different from the ones in the fruiting bodies. Accordingly, even those studies related to the beneficial properties of the fruiting body extract are not necessarily also valid for material extracted from the mycelia of A. subrufescens. 
As will be demonstrated further below, the above described macromolecular highly hydrophilic substances are of no concern to the current invention. Nevertheless, they have raised great interest in pharmacological research on the so-called medicinal mushrooms and are clearly held responsible for most of the hitherto reported biological and pharmacological activities of Agaricus subrufescens and other fungal species that are here regarded as synonyms.
In addition to the macromolecular metabolites treated in the preceding paragraphs, Agaricus subrufescens also contains triterpenoid compounds that are also sometimes referred to in the literature as “steroids”, although their chemical structures are different from those of the steroids that occur in humans. These compounds have physico-chemical and pharmacological properties quite different from those of the polysaccharides. For instance, they are almost insoluble in water, but can be readily extracted with organic solvents and thus be separated form the glucanes and other macromolecules, which will precipitate by addition of alcohol (either methanol or ethanol) to an aqueous solution, e.g. the culture filtrate as mentioned in WO 2006/133708. In addition, the triterpenoids have a rather low molecular weight in comparison to the macromolecules, and their chemical similarities to the human steroidal hormones and other steroids that occur in the human body make them more likely to exert a direct pharmacological effect, whereas the biological mode of action of the beta-glucanes and other macromolecules is believed to be due to indirect effects on the immune system, which does not necessarily involve their entering the human blood from the intestine (for overview see Chen & Seviour, Mycological Research (2007) 111: 635-652).
From fruiting bodies of A. subrufescens, Kawagishi et al. (Phytochemistry (1988) 27: 2777-2779) have reported several triterpenes with cytotoxic effects against the cancer cell line HeLaS3. Recently, Ito et al. (Oncology Rep (2008) 20: 1359-1361) identified another triterpenoid named blazein (again from Agaricus subrufescens, but using the invalid name “A. blazei”), which induced apoptosis in lung cancer cells. Such triterpenoids could also be responsible for certain other biological effects noted for the organic extracts of the fruiting bodies of A. subrufescens, such as those reported by Lund et al. (Pharma Biol (2009) 47: 910-915) who found antimicrobial activities in various extracts of the fungus (here referred to as A. brasiliensis), with the most potent activities in the 100% ethanol and weaker activities in extracts prepared by using more polar solvent mixtures. Bellini et al. (Gen Mol Biol (2008) 31: 122-127) used methanol for extraction of the mushrooms and found significant biological activities in these samples.
As the beta-glucanes are hardly soluble at all in such organic solvents and will inadvertently precipitate, they cannot be held responsible for the biological activities of non-aqueous extracts. On the other hand, Ziliotto et al. (Nut Cancer (2009) 61: 245-250) studied aqueous and various organic extracts of the same mushroom, but failed to detect any significant anticancer activities in a broad panel of malignant cell lines up to concentrations of 250 mg/ml.
Notably, the triterpene compounds from basidiocarps (i.e., fruiting bodies) of A. subrufescens all possess a regular tetracyclic triterpene carbon skeleton without any spiro-ring formation, similar to the ergostane and lanostane derivatives that are present in many other basidiomycetes (Zjawiony (J. Nat. Prod., 2004, 67(2): 300-310).
By contrast, rather characteristic and apparently specific triterpenoids have been isolated repeatedly from the cultured mycelium of A. subrufescens by Asian microbiologists and natural product chemists. Various papers have been published on this subject, for instance by Hirotani et al. (Tetrahedron Lett (1999) 40: 329-332); Hayashi et al., (Phytochemistry (2002) 59: 571-577; Tetrahedron Lett (2000) 41: 5107-5110; Phytochemistry (2002) 61: 589-595; Tetrahedron Lett (2003) 44(43): 7975-7979; Tetrahedron (2005) 61(1): 189-194). The biosynthesis of the blazeispirols was also studied by Hirotani et al. (Tetrahedron Lett (2000) 41: 6101-6104; Tetrahedron Lett (2001) 42: 5261-5264; Tetrahedron (2002) 58: 10251-10257) and is believed to arise from the ubiquitous fungal metabolite, ergosterol. The trivial names (blazeispirane and protoblazeispirane) were proposed for the two unprecedented des-A-ergostane-type carbon skeletons of the blazeispirols that have so far not been found in any other organism but the fungus that is here regarded as Agaricus subrufescens. (Notably, the blazeispirols have so far only been obtained from the cultured mycelia of this species in submersed culture). Biological activities of these compounds are widely unknown. Only Hirotani et al. (Tetrahedron Lett., (2003) 44(43): 7975-7979) reported that two derivatives of this type showed a moderate circumvention of drug resistance on mouse leukaemia P388/VCR cells. Some studies performed previously on biological activities of the extracts prepared from cultures of A. subrufescens and its synonyms might relate to the presence of blazeispirols. However, in these studies, the major active principles have not been identified conclusively, or there is even some evidence that not the genuine metabolites produced by the fungus but rather the plant-derived media constituents caused the observed biological effects of the hot water extract studied. For instance, Oh et al. (J Agric Food Chem (2010) 58: 4113-4119) have reported on hypoglycaemic activities in vivo of “semipurified” fractions from a hot water extract prepared from submerged cultures of A. subrufescens (again as “A. blazei Murill”), but the authors themselves suspected that isoflavonoids from the culture medium, rather than fungal metabolites, were the bioactive agents, because such metabolites were detected in the active fraction. The employed procedure for preparation of the active fraction, involving first extraction with hot water, followed by subsequent extraction of the resulting hot water extract with different solvents, is certainly not a feasible method for enrichment of blazeispirols and metabolites of similar polarity.
Since the addition of soybean also led to enhanced antihepatoma activities in the study by Su et al. (J Agric Food Chem (2008), 56(20): 9447-9454), and this plant is widely known to contain large amounts of isoflavonoids, it remains to be evaluated how such compounds would contribute to the biological effects observed in extracts from cultures of A. subrufescens, even though Su et al. (J Agric Food Chem (2008), 56(20): 9447-9454) used chromatography to isolate and identify blazeispirols A and C and confirmed the biological activities of these compounds against liver cancer cell lines.
Other studies such as that by Yoon et al. (J Clin Biochem Nut (2008) 43; 118-125) on antioxidative and antimutagenic effects also dealt with organic extracts from cultured mycelia of A. subrufescens, and therefore the observed activity might eventually be correlated to the presence of blazeispirols, rather than to the action of the water-soluble beta glucans.
Medimush (GlycoNova) filed patent applications all claiming the priority of DK 2005 0000881, US 2005 0690477P, DK 2006 0000115, and US 2006 0761745; the inventors worked with aqueous extracts of cultures of the genus Agaricus. In further dependent claims the applicant refers to A. blazei. It is futile to clarify the assignment of the strain because the examples clearly outline that the inventors always used water soluble compounds as they used methanol to precipitate the active compounds from the culture broth. No example presents results of organic extracts comparable those mentioned in the present invention. The disclosed culturing times are 7 days (Trametes versicolor) and 3 days (Schizophyllum commune); where the inventors explicitly point to the production of polysaccharides. The PCT applications identify bioactive agents by their biological activity and not by their chemical identity. The subsequent applications therefore are specified to the use of polysaccharides.
The disclosed procedures are not appropriate to isolate the compounds of the present invention.
Some other applications claim for a weight reducing effect using combinations of different products of plant or mushroom origin which might contain A. subrufescens: 
Primavera (PCT/US2004/012811 & U.S. Ser. No. 10/831,353; and the divisional appl. U.S. Ser. No. 12/240,236) claim for the use of mushrooms such as A. subrufescens as “liver protecting agent” or as “hunger suppressing” agent. The term mushroom is not further explained according the part of the organisms used. Consequently the common definition for “mushroom” as being a fruit body must be presumed.
Goino (Nagano, Japan, EP1736206, US20070178118) claims for a combination of a plant (Araliaceae) and an extract component which might be of the genus Agaricus, specified to A. blazei, further specified to a “hot water extract”, still more specified to an extract “containing useful saccharides such as Beta-glucan” for the use as anti-tumor agent which further exhibits several activities like hypotensive action, total cholesterol-lowering action in blood and neutral fat-lowering action, therefore might be useful as anti-hyperlipidemic agent.
There remains a need for new safe and effective compositions for treating, prophylactically and/or therapeutically, diseases, disorders or conditions that respond to LXR modulation. The problem to be solved by the present invention is therefore to find compositions or compounds useful for this purpose.